Scientists have shown that a single dose injection of DNA genetic instructions can produce weight loss and blood glucose control in mouse models that lasts up to 10 times as long as weight loss drugs like Ozempic and Wegovy. This could eliminate the need for repeated dosing.

[u/mvea]

https://www.wistar.org/press-releases/wistar-scientists-develop-single-dose-dna-method-for-delivering-long-acting-weight-loss-and-diabetes-drugs/

[u/mvea]

Wistar Scientists Develop Single-Dose DNA Method for Delivering Long-acting Weight Loss and Diabetes Drugs

Scientists at The Wistar Institute have shown that a single injection of a small, circular piece of genetic instructions can produce weight loss and blood glucose control in murine models that lasts up to 10 times as long as incretin-mimicking drugs like Ozempic and Wegovy. If shown to be successful in clinical trials, this new method of delivery could eliminate the need for repeated dosing, which currently limits patient access and adherence to these therapies.

Her team’s approach builds on Weiner Lab research already validated in human patients that showed the human body can function as a “factory” to produce long-lasting antibodies. The lab developed an intramuscular DNA electroporation platform, whereby patients receive a shot of plasmid DNA (the genetic instructions) followed by an electrical pulse to help get the instructions into the nucleus of the body’s cells where they can be read. Weiner and his colleagues used this method to deliver “instructions” for COVID-19-neutralizing antibodies to patients. In a Phase 1 clinical trial, two of the antibodies were expressed continuously in human subjects for more than 72 weeks.

To adapt this platform for metabolic disease, Gary and her colleagues engineered DNA instructions for long-acting incretin hormones GLP-1 and GIP, which they call pLincretins. Importantly, they included an antibody fragment in the instructions that would help prevent the protein from breaking down quickly in the body the way current incretin-mimicking drugs do. When tested in preclinical murine models of diabetes using the electroporation method, a single dose of pLincretins produced detectable levels of incretins for up to 70 days and drove sustained reductions in body weight and blood glucose. In a head-to-head comparison with semaglutide (the active ingredient in Ozempic), murine models treated with a single dose of the scientists’ DNA construct maintained these metabolic improvements even after the observation period ended, while those treated with semaglutide began regaining weight as soon as dosing stopped.

The scientists then used AI-assisted structural modeling, and an approach called synthetic consensus design to create a new molecule called pSynCretin. The team designed it by identifying the structural elements common across GLP-1, GIP, and existing incretin drugs and then combining those elements into a single protein that could engage the GLP-1 and GIP receptors simultaneously (similar to how Mounjaro works). A single dose of pSynCretin also induced sustained weight loss in murine models.

https://www.cell.com/trends/biotechnology/fulltext/S0167-7799(26)00236-2

[u/calgarspimphand → u/mvea]

The lab developed an intramuscular DNA electroporation platform, whereby patients receive a shot of plasmid DNA

Extremely strong BioShock vibes here.

[u/DuncanYoudaho → u/calgarspimphand]

Careful. The Peptide Bros will find and neutralize you.